Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy.

BACKGROUND & AIMS: Bepirovirsen, an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV, has been conjugated to N-acetyl galactosamine (GSK3389404) to enhance hepatocyte delivery. This dose-finding study was the first to assess GSK3389404 for chronic HBV infection. METHODS: This phase IIa, randomised, double-blind, placebo-controlled, 2-part study was conducted in 22 centres in Asia (NCT03020745). Pharmacokinetic findings from Part 1 informed Part 2 dosing. In Part 2, patients with chronic hepatitis B on nucleos(t)ide analogue therapy were randomised 11:2 to GSK3389404 (30, 60, 120 mg weekly or 120 mg bi-weekly) or placebo until Day 85. Coprimary endpoints included HBsAg response (≥1.5 log10 IU/ml reduction from baseline) rate, safety and pharmacokinetics. RESULTS: Parts 1 and 2 included 12 (9 GSK3389404, 3 placebo) and 66 patients (56 GSK3389404, 10 placebo), respectively. In Part 2, one patient each in the 60 mg weekly, 120 mg weekly and 120 mg bi-weekly arms achieved a HBsAg response. HBsAg reductions were dose-dependent (Day 85: mean 0.34 [60 mg weekly] to 0.75 log10 IU/ml [120 mg weekly]) and occurred in hepatitis B e antigen-positive and -negative patients. No patient achieved HBsAg seroclearance. 43/56 (77%) GSK3389404- and 9/10 (90%) placebo-treated patients reported adverse events. No deaths were reported. Alanine aminotransferase flares (>2x upper limit of normal) occurred in 2 GSK3389404-treated patients (120 mg weekly, 120 mg bi-weekly); both were associated with decreased HBsAg, but neither was considered a responder. GSK3389404 plasma concentrations peaked 2-4 hours post dose; mean plasma half-life was 3-5 hours. CONCLUSIONS: GSK3389404 showed an acceptable safety profile and target engagement, with dose-dependent reductions in HBsAg. However, no efficacious dosing regimen was identified. CLINICAL TRIAL NUMBER: NCT03020745. LAY SUMMARY: Hepatitis B virus (HBV) can result in chronic HBV infection, which may ultimately lead to chronic liver disease, primary liver cancer and death; HBV proteins may prevent the immune system from successfully controlling the virus. GSK3389404 is an investigational agent that targets HBV RNA, resulting in reduced viral protein production. This study assessed the safety of GSK3389404 and its ability to reduce the viral proteins in patients with chronic HBV infection. GSK3389404 showed dose-dependent reduction in hepatitis B surface antigen, with an acceptable safety profile. While no clear optimal dose was identified, the findings from this study may help in the development of improved treatment options for patients with chronic HBV infections.

Food insecurity and neurocognitive function among women living with or at risk for HIV in the United States.

BACKGROUND: Neurocognitive impairment (NCI) persists among women living with HIV. Food insecurity is also common among women and may be an important modifiable contributor of NCI. OBJECTIVE: The goal of this study was to determine the association of food insecurity with neurocognitive function among women living with or without HIV. METHODS: From 2013 to 2015, we analyzed data from a cross-sectional sample from the Women's Interagency HIV Study (WIHS). Measures included food insecurity and a comprehensive neuropsychological test battery assessing executive function, processing speed, attention/working memory, learning, memory, fluency, and motor function. We conducted multivariable linear regressions to examine associations between food insecurity and domain-specific neurocognitive performance, adjusting for relevant sociodemographic, behavioral, and clinical factors. RESULTS: Participants (n = 1,324) were predominantly HIV seropositive (68%), Black/African-American (68%) or Hispanic (16%), and low income (48% reported <$12,000/y), with a median age of 49.6 y (IQR = 43.1, 55.5). Approximately one-third (36%, n = 479) were food insecure. Food insecurity was associated with poorer executive function (b = -1.45, SE = 0.58, P ≤ 0.01) and processing speed (b = -1.30, SE = 0.59, P ≤ 0.05). HIV serostatus modified the association between food insecurity and learning, memory, and motor function (P values <0.05). Food insecurity was positively associated with learning among women living with HIV (b = 1.58, SE = 0.77, P ≤ 0.05) and negatively associated with motor function among HIV-negative women (b = -3.57, SE = 1.08, P ≤ 0.001). CONCLUSIONS: Food insecurity was associated with domain-specific neurocognitive function in women, and HIV serostatus modified associations. Food security may be an important point of intervention for ethnically diverse women with low socioeconomic status. Longitudinal studies are warranted to determine potential pathways by which food insecurity is associated with neurocognitive function among women living with or at risk for HIV.

Serious quit attempts and cessation implications for Asian American male smokers.

INTRODUCTION: Smoking prevalence remains high among Asian American immigrant men, particularly those with limited English proficiency. Understanding ways to promote serious quit attempts (defined as a quit attempt lasting at least 24 h) could be crucial for reducing tobacco-related health disparities in this population. This study examines correlates of serious past year quit attempts among Chinese and Vietnamese American male daily smokers. METHODS: Baseline survey data were collected between 2015 and 2017 from a lifestyle intervention trial (N = 340 Chinese and Vietnamese male daily smokers). Data analysis was conducted in 2019. Multivariable logistic regression analysis was used to identify factors associated with serious past year quit attempts. RESULTS: Less than half (43.2%) of the study participants had at least one serious past year quit attempt. Significant correlates of serious quit attempts included utilizing evidence-based methods (OR = 12.83, 95% CI 5.17-31.84) or other methods (OR = 3.92, 95% CI 3.92-13.73) to facilitate quitting compared to those who did not attempt to quit. Also, participants who had a physician encounter in the past year were more likely to have had a serious quit attempt (OR = 2.25, 95% CI 1.12-4.53). Discussing smoking during a past year doctor's visit, however, was not a significant correlate of serious quit attempts. CONCLUSIONS: Our findings underscore the importance of promoting the use of smoking cessation resources, and potentially utilizing healthcare encounters to facilitate cessation. Investigations are warranted to understand better how patient-physician interactions can enhance smoking cessation.

Injecting-related trust, cooperation, intimacy, and power as key factors influencing risk perception among drug injecting partnerships.

Sharing of injection drug use paraphernalia is a dyadic process linked to the transmission of HIV and hepatitis C virus (HCV). Despite this, limited research exists identifying specific dyadic interpersonal factors driving injecting partners' engagement in needle/syringe and ancillary injecting equipment sharing among young adults. Using semi-structured in-depth interview data collected between 2014 and 2015 from twenty-seven people who inject drugs (PWID), we applied an inductive approach to identify key injection drug-related interpersonal factors and developed a conceptual model integrating the findings based on interdependence theory. Interactions between injecting partners resulted in varying levels of injecting-related trust, cooperation, intimacy, and power. These factors interacted to collectively influence the type and level of risk perceived and enacted by injecting partners. The relationship between these injecting-related interpersonal factors, on the one hand, and risk perception on the other was dynamic and fluctuated between actions that protect the self (person-centered) and those that protect the partnership (partnership-centered). These findings indicate that the interpersonal context exerts substantial influence that shapes risk perception in all types of injecting partnerships. Partnership-focused prevention strategies should consider the dynamics of trust, cooperation, intimacy, and power, in characterizing dyadic risk perceptions and in understanding risky injecting practices among PWID.

The Role of the Primary Romantic Relationship in HIV Care Engagement Outcomes Among Young HIV-Positive Black Men Who Have Sex with Men.

The primary romantic relationship plays a fundamental role in health maintenance, but little is known about its role in HIV care engagement among young Black men who have sex with men (MSM) living with HIV. We examined how HIV care engagement outcomes (i.e., having a primary healthcare provider, receiving HIV treatment, taking antiretroviral medication, and medication adherence) vary by partnership status (single vs. concordant-positive vs. discordant) in a sample of young Black MSM living with HIV. Results showed mixed findings. Partnership status was significantly associated with HIV care engagement, even after adjusting for individual, social, and structural factors. While partnered men were consistently more likely than their single counterparts to have a regular healthcare provider, to receive recent treatment, and to have ever taken antiretroviral medication, they were less likely to report currently receiving antiretroviral therapy. Moreover, men with a discordant partner reported better adherence compared to men with a concordant or no partner. The association between partnership status and HIV care engagement outcomes was not consistent across the stages of the HIV Care Continuum, highlighting the complexity in how and why young Black men living with HIV engage in HIV healthcare. Given the social context of HIV disease management, more research is needed to explicate underlying mechanisms involved in HIV care and treatment that differ by relational factors for young Black MSM living with HIV.